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      Potassium-Sparing Renal Effects of Trimethoprim and Structural Analogues

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          Background/Aims: The antibiotic antagonists of folic acid trimethoprim, tetroxoprim, pyrimethamine and their antineoplastic analogue methotrexate have structural characteristics in common with the potassium-sparing diuretic triamterene. They may, therefore, share with triamterne potassium-sparing renal effects. Methods: Clearance studies were performed on anesthetized male Sprague-Dawley rats, and the drug effects on glomerular filtration rate and on urinary excretion of sodium, chloride, and potassium were studied. Results: Trimethoprim and tetroxoprim, injected intravenously at doses ranging from 0.3 to 30 mg/kg, induced dose-dependent natriuretic and antikaliuretic renal effects, whereas pyrimethamine at doses ranging from 1 to 10 mg/kg and methotrexate at doses ranging from 10 to 50 mg/kg did not affect urinary sodium and potassium excretion. An antikaliuretic effect was also observed after application of the structurally related antiprotozoal compound pentamidine at doses ranging from 3 to 10 mg/kg. In contrast to trimethoprim and tetroxoprim, the antikaliuresis was accompanied by a marked decrease of urinary sodium and chloride excretion at all of the doses tested. At 10 mg/kg, pentamidine induced a pronounced fall of the glomerular filtration rate (by 43.5%). Conclusions: Trimethoprim and tetroxoprim share with potassium-sparing diuretics natriuretic and antikaliuretic renal effects which may be caused by similar mechanisms in the distal nephron, whereas pyrimthamine and methotrexate do not. A depression of renal hemodynamics is an important factor involved in the antikaliuretic effect of pentamidine.

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          Brief report: trimethoprim-induced hyperkalemia in a patient with AIDS.


            Author and article information

            S. Karger AG
            September 2000
            30 August 2000
            : 86
            : 1
            : 70-78
            Department of Pharmacology and Toxicology, Rheinisch-Westfälische Technische Hochschule, Aachen, Germany
            45715 Nephron 2000;86:70–78
            © 2000 S. Karger AG, Basel

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            Page count
            Figures: 8, Tables: 2, References: 23, Pages: 9
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